Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states

Nat Genet. 2017 Feb;49(2):213-222. doi: 10.1038/ng.3734. Epub 2016 Dec 12.

Abstract

The opposition between Polycomb repressive complexes (PRCs) and BAF (mSWI/SNF) complexes has a critical role in both development and disease. Mutations in the genes encoding BAF subunits contribute to more than 20% of human malignancies, yet the underlying mechanisms remain unclear, owing largely to a lack of assays to assess BAF function in living cells. To address this, we have developed a widely applicable recruitment assay system through which we find that BAF opposes PRC by rapid, ATP-dependent eviction, leading to the formation of accessible chromatin. The reversal of this process results in reassembly of facultative heterochromatin. Surprisingly, BAF-mediated PRC eviction occurs in the absence of RNA polymerase II (Pol II) occupancy, transcription, and replication. Further, we find that tumor-suppressor and oncogenic mutant BAF complexes have different effects on PRC eviction. The results of these studies define a mechanistic sequence underlying the resolution and formation of facultative heterochromatin, and they demonstrate that BAF opposes PRC on a minute-by-minute basis to provide epigenetic plasticity.

MeSH terms

  • Carcinogenesis / genetics*
  • Chromatin / genetics
  • DNA Replication / genetics
  • DNA-Binding Proteins / genetics*
  • Epigenesis, Genetic / genetics
  • Heterochromatin / genetics*
  • Humans
  • Mutation / genetics
  • Nuclear Proteins / genetics*
  • Polycomb-Group Proteins / genetics*
  • RNA Polymerase II / genetics
  • Transcription, Genetic / genetics

Substances

  • BANF1 protein, human
  • Chromatin
  • DNA-Binding Proteins
  • Heterochromatin
  • Nuclear Proteins
  • Polycomb-Group Proteins
  • RNA Polymerase II